Investigation of the molecular mechanisms of the effect of the NO donor pentaerytrithyltetranitrate on the regulation of cellular stress
Preeclampsia and fetal growth restriction are pregnancy complications characterized by placental and endothelial dysfunction. In a clinical study, we have shown that the NO donor pentaerythrityltetranitrate (PETN) reduces the rate of pregnancy-induced hypertension in high-risk pregnancies by 30 % and simultaneously lowers the concentration of endothelial activating cytokines in the mothers' blood. Translationally, we were able to show that in stressed endothelial and trophoblast cells in the presence of PETN, the formation of reactive oxygen species and cellular dysfunction in response to oxidative stress is reduced. It is known from literature that PETN induces the expression of the antioxidant enzyme heme-oxigenase-1 (HO-1) in endothelial cells. The exact molecular mechanisms of the demonstrated effect of PETN have not yet been investigated. In this project, the signaling cascades stimulated by PETN will be identified by omic analysis and verified by Western blot. The clarification of the mechanisms of action of PETN is the basis for the identification of further indications for the use of PETN in diseases associated with endothelial dysfunction in humans.